Aside from providing buoyancy and protection for brain, the functional significance of cerebrospinal fluid (CSF) remains poorly understood. The objective of this study is to evaluate the hypothesis that CSF functions as an excretory system for brain by following the time course and route of removal from brain of test substances injected into identified intracerebral sites. Test compounds would include radioisotopes, to follow material efflux quantitatively, and horseradish peroxidase, to define anatomical pathways of exchange. Results would relate to the relative importance of CSF and of cerebral capillaries as routes of material excretion from brain, to mechanisms of molecular efflux from brain (convection, diffusion or carrier-mediated transport), and to the specificity of carrier-mediated transport systems at the choroid plexus and blood-brain barrier for organic acids (including prostaglandins and acid monoamine metabolites). Mathematical models predicting rates and routes of removal from brain would be developed and control studies would continue to evaluate the technique of quantitative intracerebral injection (as developed in this laboratory) for studies of material efflux from the central nervous system. Methods include quantitative intracerebral injection, ventriculo-cisternal perfusion, and substrate accumulation by isolated choroid plexus.